Hox complex genes are key developmental regulators highly conserved throughout evolution. The encoded proteins share a 60-amino-acid DNA-binding motif, the homeodomain, and function as transcription factors to control axial patterning. An important question concerns the nature and function of genes acting downstream of Hox proteins. This review focuses on Drosophila, as little is known about this question in other organisms. The noticeable progress gained in the field during the past few years has significantly improved our current understanding of how Hox genes control diversified morphogenesis. Here we summarise the strategies deployed to identify Hox target genes and discuss how their function contributes to pattern formation and morphogenesis. The regulation of target genes is also considered with special emphasis on the mechanisms underlying the specificity of action of Hox proteins in the whole animal.

The transcription factor dMyc is the sole Drosophila ortholog of the vertebrate c-myc protooncogenes and a central regulator of growth and cell-cycle progression during normal development. We have investigated the molecular basis of dMyc function by analyzing its interaction with the putative transcriptional cofactors Tip48͞Reptin (Rept) and Tip49͞Pontin (Pont). We demonstrate that Rept and Pont have conserved their ability to bind to Myc during evolution. All three proteins are required for tissue growth in vivo, because mitotic clones mutant for either dmyc, pont, or rept suffer from cell competition. Most importantly, pont shows a strong dominant genetic interaction with dmyc that is manifested in the duration of development, rates of survival and size of the adult animal and, in particular, of the eye. The molecular basis for these effects may be found in the repression of certain target genes, such as mfas, by dMyc:Pont complexes. These findings indicate that dMyc:Pont complexes play an essential role in the control of cellular growth and proliferation during normal development.repression ͉ transcription M yc proteins are essential regulators of growth, proliferation, and apoptosis in metazoans (1-3). These proteins act as transcription factors to control the expression of numerous target genes involved in growth, metabolism, and other processes (4-7). Less is known about the molecular mechanism that allows Myc to control the expression of these targets. In recent years, different modes of gene activation by Myc have been proposed, notably recruitment of chromatin remodelers (8), histone acetylases (e.g., ref. 9), or RNA pol II kinases (10), but the physiological relevance of these different factors for Myc-dependent biological functions needs to be demonstrated. We therefore set out to study the mechanisms of Myc-controlled growth and proliferation during normal development by using Drosophila as a model system. Initially, we focused on the interaction of Myc with two specific components of cofactor complexes, Tip48 and Tip49, because of the availability of null mutations in the corresponding genes [called reptin (rept) and pontin (pont) in flies, respectively].Tip48 and Tip49 are closely related proteins that show a high similarity to the bacterial ATP-dependent AAAϩ super family DNA helicase RuvB. Orthologs of Tip48 and Tip49 have been identified in plants, yeast, and animals (e.g., refs. 11 and 12). Different observations strongly suggest that one major function of the Tip proteins resides in the control of transcription. Initially, vertebrate Tip49 was found to be a Tata-binding protein-interacting protein (13-16); later Tip48 and Tip49 were also shown to interact physically with the different transcription factors ␤-catenin (11, 14), c-Myc (12), E2F1 (only Tip49) (17), and ATF2 (only Tip48) (18), raising the possibility that the Tip proteins could bridge basic transcription machinery and sequence-specific activators. Both proteins were also purified as part of several multiprotein complexes involved i...

Pontin (Pont) and Reptin (Rept) are paralogous ATPases that are evolutionarily conserved from yeast to human. They are recruited in multiprotein complexes that function in various aspects of DNA metabolism. They are essential for viability and have antagonistic roles in tissue growth, cell signalling and regulation of the tumour metastasis suppressor gene, KAI1, indicating that the balance of Pont and Rept regulates epigenetic programmes critical for development and cancer progression. Here, we describe Pont and Rept as antagonistic mediators of Drosophila Hox gene transcription, functioning with Polycomb group (PcG) and Trithorax group proteins to maintain correct patterns of expression. We show that Rept is a component of the PRC1 PcG complex, whereas Pont purifies with the Brahma complex. Furthermore, the enzymatic functions of Rept and Pont are indispensable for maintaining Hox gene expression states, highlighting the importance of these two antagonistic factors in transcriptional output.